INVESTIGADORES
GALIGNIANA Mario Daniel
congresos y reuniones científicas
Título:
Subcellular localization of FKBP51 is modified in a redox-sensitive manner
Autor/es:
DE LEO SA, GALLO LI, ERLEJMAN AG, GALIGNIANA MD
Reunión:
Congreso; VIII Meeting of the Society Free Radical Biology and Medicine; 2013
Resumen:
The immunophilin FKBP51 was first described as a cytosolic
regulator of steroid receptors. Recently, we demonstrated that FKBP51 is also
mitochondrial and translocates to the nucleus upon the onset of oxidative-stress.
In this study, we first compared the subcellular localization of FKBP51 in normal
and cancer cell types (HeLa, U2OS, MCF7, Caco-2, HepG-2, T47D) by confocal
microscopy and found that, in contrast to the mitochondrial localization
exhibited by normal cells, FKBP51 shows preponderant nuclear (and nucleolar) localization.
This paralleled increased H2DCFDA (2',7'-dichlorodihydrofluorescein-diacetate)
cell staining, suggesting a dependence with the redox-status
of the cell. Accordingly, glutathione treatment reversed FKBP51 localization.
In HEK293-51 cells (an FKBP51 overexpressing cell line), the nuclear
accumulation of the immunophilin was greater than in wild-type cells (WT). Even
though H2O2 (100mM for 24h)
diminished the number of viable cells (MTT-viability test), the HEK293-51 cell
line showed significantly greater viability (70% vs. 60% WT). Overexpression of
FKBP52 (a natural FKBP51 competitor) decreased cell viability to 34% in
response to H2O2. We conclude that: a)-FKBP51 subcellular
localization depends on the redox-status of the cell, b)-its overexpression protects cells against the
deleterious action of oxidative stress, and c)-the FKBP51/FKBP52 expression
balance could regulate cell survival in response to oxidative damage.